Chronic hepatitis C is the leading cause of chronic liver disease and cirrhosis in the United States and is now the leading cause for liver transplantation due to end-stage liver disease. Approximately 1.8% of population (4 million) in the United States have antibody to hepatitis C virus (anti-HCV) and approximately 2.7 million Americans have evidence of chronic infection. The prevalence of antibody to HCV is higher among African Americans (3.2%) than among the non-Hispanic whites (1.8%). Treatment of chronic hepatitis C remains problematical and unsatisfactory. Interferon (IFN) monotherapy given as three times weekly injections has been shown to have biochemical, virological and histological beneficial effects. However, sustained virological response (SVR) is seen in only a minority of patients (6-16%). Treatment with combination of IFN + and ribavirin for 24 or 48 weeks results in SVR rates of up to 35 to 43% respectively. Very limited published data is currently available on the impact of race on response to antiviral therapy in patients with chronic hepatitis C. Most available reports show that African Americans have a significantly lower SVR when compared to non-Hispanic whites with all treatment regimens. We are proposing a multicenter, controlled clinical trial of combination therapy of pegylated interferon + ribavirin for African Americans and non-Hispanic whites chronically infected with HCV genotype 1 virus. Treatment will be administered for a total duration of 48 weeks with a 48-week follow-up post completion of therapy. A total of 400 patients with equal numbers of Caucasians and African Americans (200 in each group) will be enrolled into this study. The primary end-point of this trial is to determine rate of SVR among African Americans and non-Hispanic whites. In addition, factors predictive for a favorable response and patterns of virological response will also be assessed in the two racial groups. The objectives of this trial are to evaluate: (a) the rates of SVR among African Americans and non-Hispanic Whites with chronic hepatitis C after treatment with combination therapy using pegylated interferon and ribavirin for 48 weeks; (b) the factors that are predictive of a SVR to combination therapy in each of the two racial groups and factors associated with poorer response in African Americans and (c) the patterns of virological response (including viral kinetics) early during treatment and determine if different responses predict the ultimate outcome (sustained response, relapse or a lack of response) in each of the two racial groups. The findings of this study will allow us to develop specific algorithms to predict rates of SVR to therapy among African Americans based on their pre-treatment characteristics and patterns of virological response during therapy.